Substitution reactions

Halogenoalkanes are attacked by nucleophilic reagents (reagents seeking a positive charge) and undergo substitution of the halide ion by the nucleophile.

The general reaction scheme is as follows:

R-X + Nu^- → R-Nu + X^-

Where R is an alkyl chain, X is the halide ion and Nu the nucleophile.

Reaction with hydroxide ions

Halogenoalkanes undergo nucleophilic substitution on warming with dilute alkali, making alcohols:

chloroethane + sodium hydroxide → ethanol + sodium chloride
CH₃CH₂Cl + NaOH → CH₃CH₂OH + NaCl

The hydroxide ion is the nucleophile and the chloride ion is said to be the 'leaving group'.

Nucleophilic substitution with cyanide ions, CN-

The cyanide ion, CN- is a good nucleophile and reacts with haloalkanes producing nitriles.

potassium cyanide + bromoethane → ethanonitrile + potassium bromide
KCN + CH₃CH₂Br → CH₃CH₂CN + KBr

This is a useful reaction for increasing the chain length by one carbon atom. Nitriles, themselves can be reduced to amines by hydrogen/nickel catalyst at 250ºC.

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Mechanisms of nucleophilic substitution

Nucleophilic substitution with cyanide ions

Step 1: The cyanide ion attacks at the partially positive carbon of the dipole, making a high energy transition state.

Step 2: The bromine atom leaves with its bonding electrons as a bromide ion

Step 3. The final product is a nitrile.

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Nucleophilic substitution of ammonia, NH₃

Ammonia reacts with haloalkanes producing amines. The mechanism once again depends on whether the haloalkane is 1º, 2º or 3.

ammonia + bromoethane → ethylamine + hydrogen bromide
NH₃ + CH₃CH₂Br → CH₃CH₂NH₂ + HBr

Mechanism

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Primary, secondary and tertiary haloalkanes

Nucleophilic substitution proceeds via different mechanisms, depending on whether the haloalkane is primary, secondary or tertiary. There are two distinct mechanisms, one for primary and one for tertiary. The mechanism followed by secondary haloalkanes is thought to be a mixture of the other two.

Primary halogenoalkanes

The nucleophile attacks the partially positive carbon that is attached to the halogen atom. This goes through a high energy transition state in which the carbon atom is associated with the incoming nucleophile as well as the outgoing halide ion.

Bimolecular Nucleophilic Substitution

Step 1: The hydroxide ion is attracted towards the partially positive carbon atom.

Step 2: A high energy transition state develops.

Step 3. The chloride ion (leaving group) breaks off leaving the hydroxide ion bonded to the alkyl group.

The mechanism for nucleophilic substitution involves two particles, the haloalkane and a nucleophile in the initial stage of reaction. For this reason it is said to be 'bimolecular'. S_N2 stands for substitution - nucleophilic - bimolecular.

Tertiary halogenoalkanes

Tertiary haloalkanes react via a different mechanism. The tertiary carbonium ion formed by loss of a halide ion from the halogenoalkane is sufficiently stable to exist independently. The tertiary halalkane is in equilibrium with this carbonium ion:

(CH₃)₃C-Br ⇋ (CH₃)₃C⁺ + Br^-
2-bromomethylpropane ⇋ tertiary carbonium ion + bromide ion

The nucleophile can attack the tertiary carbonium ion as soon as it is formed. The rate determining step is the dissociation of the tertiary haloalkane, which only involves one species. For this reason it is said to be unimolecular. sN1

Unimolecular Nucleophilic Substitution

Step 1: The bromine atom first breaks off as an ion, leaving a tertiary carbonium ion

Step 2: The tertiary carbonium ion is attacked by the hydroxide nuclophile.

Step 3. The final product is a tertiary alcohol.

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